Dual-filament regulation of contraction in slow skeletal muscle

The control of activation and relaxation of slow twitch muscles is not understood at the molecular level, despite the importance of this muscle type for maintaining the posture of the body in everyday life. Slow muscles become weak in disease and in the elderly, reducing quality of life. A better understanding of the normal mechanisms of regulation of contraction in slow muscle could underpin the design and screening of novel therapeutics for muscle weakness. Synchrotron-based small-angle X-ray diffraction and interference is the most powerful technique to attain that understanding in intact muscles in physiological conditions. We will use it to determine the time course of the activation and deactivation of the thick and thin filaments in slow muscles using time-resolved control of muscle load to separate the effects of calcium and mechano-sensing on filament activation states. We expect the results to produce a step change in understanding the regulation of slow muscle.